Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

Objective:To prepare novel dental composite resins using zinc(Zn)-and nitrogen(N)-modified titanium dioxide(TiO?)nanoparticles(NPs)and mesoporous alumina(Al?O?,r type,20 mm)NPs as reinforcing fillers,systematically evaluating their antibacterial activity,mechanical strength,basic performance,and biosafety to obtain the dental composite resins with excellent antibacterial activity and mechanical strength.Methods:Zn-N-TiO? NPs and mesoporous Al?O? NPs were added into a resin matrix at varying mass ratios to prepare five composite resins:control group(no filler),group 0(Zn-N-TiO?∶Al?O?=1∶0),group 1(Zn-N-TiO?∶Al?O?=1∶1),group 2(Zn-N-TiO?∶Al?O?=1∶2),and group 3(Zn-N-TiO?∶Al?O?=1∶3).Plate colony counting method was used to detect the number of adhered bacteria on composite resin surfaces in various groups and calculate the antibacterial rate;scanning electron microscope(SEM)was used to observe the morphology of adhered bacteria in various groups;universal testing machine was used to measure flexural strength(FS)and elastic modulus(EM)of composite resins in various groups;SEM was used to observe fracture surface morphology of composite resins in various groups;microhardness tester was used to determine Vickers microhardness of the composite resins in various groups;Fourier transform infrared spectroscope was used to detect double bond conversion rate(DC)after 20 s photocuring and calculate curing depth;water contact angle meter was used to measure water contact angle(WCA),water sorption property(WSP),and water solubility level(WSL)of composite resins in various groups;cell counting kit-8(CCK-8)method was used to evaluate relative growth rate(RGR)of the mouse fibroblast L-929 cells cultured in composite resin extracts on days 1,3,and 5 and determine in vitro cytotoxicity grade.Results:The plate colony counting results showed that compared with control group,the colony counts on agar plates in the other groups were significantly reduced,with group 1 showing the lowest count.The SEM images results showed densely distributed and morphologically intact Streptococcus mutans in control group;small clusters of bacteria with depressed cell membranes in group 0 and group 3;sparsely distributed bacteria with obvious membrane shrinkage and cytoplasmic leakage in group 1 and group 2.No statistically significant difference in colony counts was found between group 1 and group 2(P>0.05),but both were lower than the other groups(P<0.05).All the composite resins in experimental groups exhibited>85%antibacterial rates,with group 1 and group 2 exceeding 99%.The composite resins in group 0 showed the lowest FS.With addition of mesoporous Al?O?,the FS of the composite resin in group 1 and group 2 were significantly increased,with the composite resin in group 2 showing the highest FS among all groups.Although the FS of the composite resin in group 3 was lower than that in group 2,but it remained higher than other groups(P<0.05).The SEM images results showed that in control group,the smooth-surfaced sillicon dioxide(SiO?)particles exhibited clear fracture interfaces with resin matrix,with>50%particle exposure;the composite resin in group 0 showed similar morphology and large Zn-N-TiO? agglomerates with tight filler-matrix bonding;the composite resin in group 1,2,and 3 showed resin adhesion to SiO? surfaces(<50%particle exposure)and uneven fracture surfaces.Fractured SiO? spheres were observed in group 2.Filler distribution was uniform in group 1 and group 2,while the minor NP agglomeration occurred in group 3.The composite resin in control group showed the lowest EM.The EM was significantly improved in experimental groups,with group 3 having the highest value.Group 0 exhibited the lowest Vickers microhardness,showing statistically significant differences among other groups(P<0.05).The Vickers microhardness of the composite resion was gradually increased with the rising of Al?O? content.The resins in group 2 and group 3 achieved>45 HV hardness,representing increases of 29.73%and 33.82%compared with control group,and 51.34%and 56.28%compared with group 0.No significant differences in DC of the composite resin were found among groups(P>0.05).The depth of cure for all composite resin groups exceeded 4 mm,with no significance differences observed between various groups(P>0.05).The composite resin in group 0 showed the smallest WCA.The hydrophobicity of the composite resion was increased with the rising of Al?O? content,but all the WCA values remained<80°.The composite resin in group 3 had the largest WCA without statistical significance compared with group 2(P>0.05).Filler incorporation reduced the water sorption/solubility.The composite resin in the CCK-8 assay results showed the composite resins in all groups had RGR>75%,meeting in vitro safety standards.Conclusion:Reinforcing fillers impart superior antibacterial activity and mechanical properties to composite resins.Under experimental conditions,group 2 composite resin achieves optimal comprehensive performance in antibacterial efficacy and mechanical strength,demonstrating promising clinical application potential.

Objective To retrieve,evaluate and synthesize the best evidence for nutritional management in patients with acute-on-chronic liver failure.Methods Evidence on nutritional management of patients with acute-on-chronic liver failure was systemically retrieved from the clinical decision support systems,guideline websites,professional association websites and databases,such as Cochrane Library,Joanna Briggs Institute,PubMed,Embase,CINAHL,Web of Science,VIP database,CNKI and CBM,including clinical decisions,guidelines,expert consensuses,evidence summaries and systematic reviews from inception to July 16,2024.Researchers trained in evidence-based nursing used authoritative tools to evaluate the methodological quality of the literature,and extracted and synthesized evidence according to the theme.Results A total of 13 articles were included,including 1 clinical decision,8 guidelines,and 4 expert consensuses.The best evidence included 26 pieces of evidence in 6 areas,namely the nutrition support team,nutritional assessment,energy and protein intake,oral nutrition support,enteral and parenteral nutrition support,and management of complications.Conclusion This study summarizes the best evidence for nutritional management in patients with acute-on-chronic liver failure,which can provide a basis for their standardized management.Medical staff should evaluate the availability of evidence from multiple perspectives when applying it.

Objective:To explore the efficacy and safety of negative-pressure wound therapy (NPWT) in treating infected wounds in orthopedic trauma patients.Methods:China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Cochrane Library, and CINAHL were searched for randomized controlled trials (RCT) and cohort studies examining the impact of NPWT on wound healing in orthopedic trauma infections. The retrieval time was from the establishment of the databases to October 2024. RevMan 5.4 software was used for Meta-analysis. The patients were divided into two groups according to different treatment methods: the intervention group, treated with NPWT, and the control group, treated with conventional treatment. The observed indicators included clinical efficacy, wound healing quality, length of hospital stay, wound healing time, incidence of complications, secondary surgery rate, and duration of antibiotic use. Publication bias analysis was performed on the observed indicators through Begg and Egger tests.Results:A total of 13 studies were included, comprising 11 RCT and 2 cohort studies, involving a total of 3 538 patients, with 1 762 in the intervention group and 1 776 in the control group. The meta-analysis results indicated that the intervention group had better clinical efficacy ( OR=7.08, 95% CI 5.31, 9.45, P<0.01), higher wound healing quality ( MD=4.15, 95% CI 3.99, 4.32, P<0.01), shorter length of hospital stay ( MD=-13.38, 95% CI -14.39, -12.38, P<0.01), shorter wound healing time ( MD=-8.11, 95% CI -10.22, -6.00, P<0.01), lower incidence of complications, lower secondary surgery rate ( OR=0.22, 95% CI 0.09, 0.57, P<0.01), and shorter duration of antibiotic use ( MD=-7.61, 95% CI -8.06, -7.16, P<0.01) when compared with the control group. No significant publication bias was observed in the aforementioned indicators ( P>0.05). Conclusion:Compared with the conventional treatment, NPWT can enhance the clinical efficacy and wound healing quality of infected wounds in orthopedic trauma patients, shorten length of hospital stay and wound healing time, reduce the incidence of complications and secondary surgery rates, and shorten the duration of antibiotic use.

OBJECTIVES: Pyroptosis plays a critical role in tubulointerstitial lesions of diabetic kidney disease (DKD). Annexin A2 (ANXA2) is involved in cell proliferation, apoptosis, and adhesion and may be closely related to DKD, but its specific mechanism remains unclear. This study aims to investigate the role and molecular mechanism of ANXA2 in high glucose-induced pyroptosis of renal tubular epithelial cells, providing new targets for DKD prevention and treatment. METHODS: Human renal tubular epithelial HK-2 cells were divided into a normal glucose group (5.5 mmol/L), a high glucose group (30.0 mmol/L), and a osmotic control group (24.5 mmol/L mannitol+5.5 mmol/L glucose). ANXA2 expression was modulated by overexpression of plasmids and small interfering RNA (siRNA). Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, apoptosis by flow cytometry, and ANXA2, p50, and p65 subcellular localization by immunofluorescence. Western blotting was employed to detect α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type IV (Col-IV). Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting were used to analyze nuclear factor-κB (NF-κB) subunits p50/p65 and the pyroptosis pathway factors NLR family Pyrin domain containing 3 (NLRP3), caspase-1, inferleukin (IL)-1β, and IL-18. Protein interactions between ANXA2 and p50/p65 were examined by co-immunoprecipitation, while chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to examine NF-κB binding to the ANXA2 promoter. RESULTS: High glucose upregulated ANXA2 expression and promoted its nuclear translocation (P<0.01). High glucose reduced cell proliferation, increased apoptosis, and elevated α-SMA, FN, and Col-IV expression (all P<0.05); ANXA2 overexpression aggravated these effects (all P<0.05), while ANXA2 knockdown reversed them (all P<0.05). High glucose activated NF-κB and increased NLRP3, caspase-1, L-1β, and IL-18 mRNA and protein expression (all P<0.05); ANXA2 overexpression further enhanced this, whereas knockdown suppressed NF-κB activation and downstream factors (all P<0.05). Co-immunoprecipitation confirmed ANXA2 directly binds the NF-κB subunit p65. ChIP assays revealed p65 binds specifically to ANXA2 promoter regions (ChIP-2, ChIP-4, and ChIP-6), and luciferase activity in corresponding mutant constructs (M2, M4, and M6) was significantly increased versus controls (all P<0.05), confirming positive transcriptional regulation of ANXA2 by p65. CONCLUSIONS ANXA2 and NF-κB form a positive feedback loop that sustains NLRP3 inflammasome activation, promotes pyroptosis pathway activation, and aggravates high glucose-induced renal tubular epithelial cell injury. Targeting ANXA2 or blocking its interaction with p65 may be a novel strategy to slow DKD progression.
Humans ; Pyroptosis/drug effects* ; Annexin A2/physiology* ; Epithelial Cells/cytology* ; Kidney Tubules/cytology* ; Glucose/pharmacology* ; Diabetic Nephropathies/metabolism* ; NF-kappa B/metabolism* ; Cell Line ; Cell Proliferation ; Transcription Factor RelA/metabolism* ; Feedback, Physiological

Objective:To investigate transition pattern of health status among middle-aged and elderly population in China based on frailty index.Methods:In this retrospective cohort study, middle-aged and elderly people were selected from the China Health and Retirement Longitudinal Study (CHARLS) in 2011; and 1 434 subjects were followed up to 2015. The frailty index was calculated from the prevalence of chronic diseases, daily activity ability and blood biomarkers, and the frailty state was divided by quartiles of the frailty index. Markov models were constructed to determine the transition probabilities of different frailty states.Results:The mean age of the 1 434 subjects was (59.0±9.4) years and the mean frailty index was 0.11±0.05. In the healthy individuals, 63.0% remained healthy after a four-year follow-up; during the same follow-up period, 40.9% of the mildly frail individuals and 23.0% of the moderately frail individuals remained in their baseline frailty status. Increasing age leaded to a gradual increase in the probability of the population shifting to a severely frailty state. Women were more likely to shift to severe frailty status than men (0.029 vs 0.019, Z=3.03, P=0.002). Conclusion:Among middle-aged and elderly population in China, the transition of health states follows a pattern where higher frailty levels are associated with lower stability. Advanced age and female gender are identified as risk factors for progression to severe frailty.

Objective:To explore the efficacy and safety of negative-pressure wound therapy (NPWT) in treating infected wounds in orthopedic trauma patients.Methods:China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Cochrane Library, and CINAHL were searched for randomized controlled trials (RCT) and cohort studies examining the impact of NPWT on wound healing in orthopedic trauma infections. The retrieval time was from the establishment of the databases to October 2024. RevMan 5.4 software was used for Meta-analysis. The patients were divided into two groups according to different treatment methods: the intervention group, treated with NPWT, and the control group, treated with conventional treatment. The observed indicators included clinical efficacy, wound healing quality, length of hospital stay, wound healing time, incidence of complications, secondary surgery rate, and duration of antibiotic use. Publication bias analysis was performed on the observed indicators through Begg and Egger tests.Results:A total of 13 studies were included, comprising 11 RCT and 2 cohort studies, involving a total of 3 538 patients, with 1 762 in the intervention group and 1 776 in the control group. The meta-analysis results indicated that the intervention group had better clinical efficacy ( OR=7.08, 95% CI 5.31, 9.45, P<0.01), higher wound healing quality ( MD=4.15, 95% CI 3.99, 4.32, P<0.01), shorter length of hospital stay ( MD=-13.38, 95% CI -14.39, -12.38, P<0.01), shorter wound healing time ( MD=-8.11, 95% CI -10.22, -6.00, P<0.01), lower incidence of complications, lower secondary surgery rate ( OR=0.22, 95% CI 0.09, 0.57, P<0.01), and shorter duration of antibiotic use ( MD=-7.61, 95% CI -8.06, -7.16, P<0.01) when compared with the control group. No significant publication bias was observed in the aforementioned indicators ( P>0.05). Conclusion:Compared with the conventional treatment, NPWT can enhance the clinical efficacy and wound healing quality of infected wounds in orthopedic trauma patients, shorten length of hospital stay and wound healing time, reduce the incidence of complications and secondary surgery rates, and shorten the duration of antibiotic use.

Objective:To investigate transition pattern of health status among middle-aged and elderly population in China based on frailty index.Methods:In this retrospective cohort study, middle-aged and elderly people were selected from the China Health and Retirement Longitudinal Study (CHARLS) in 2011; and 1 434 subjects were followed up to 2015. The frailty index was calculated from the prevalence of chronic diseases, daily activity ability and blood biomarkers, and the frailty state was divided by quartiles of the frailty index. Markov models were constructed to determine the transition probabilities of different frailty states.Results:The mean age of the 1 434 subjects was (59.0±9.4) years and the mean frailty index was 0.11±0.05. In the healthy individuals, 63.0% remained healthy after a four-year follow-up; during the same follow-up period, 40.9% of the mildly frail individuals and 23.0% of the moderately frail individuals remained in their baseline frailty status. Increasing age leaded to a gradual increase in the probability of the population shifting to a severely frailty state. Women were more likely to shift to severe frailty status than men (0.029 vs 0.019, Z=3.03, P=0.002). Conclusion:Among middle-aged and elderly population in China, the transition of health states follows a pattern where higher frailty levels are associated with lower stability. Advanced age and female gender are identified as risk factors for progression to severe frailty.